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Title 

Iron overload-induced calcium signals modulate mitochondrial fragmentation in HT-22 hippocampal neuron cells

Authors 

D G LeeJ ParkH S LeeSang-Rae LeeD S Lee

Publisher 

Elsevier

Issue Date 

2016

Citation 

Toxicology, vol. 365, no. 0, pp. 17-24

Keywords 

CalcineurinCalciumIron overloadMitochondrial dynamicsNeurotoxicity

Abstract 

Iron is necessary for neuronal functions; however, excessive iron accumulation caused by impairment of iron balance could damage neurons. Neuronal iron accumulation has been observed in several neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Nevertheless, the precise mechanisms underlying iron toxicity in neuron cells are not fully understood. In this study, we investigated the mechanism underlying iron overload-induced mitochondrial fragmentation in HT-22 hippocampal neuron cells that were incubated with ferric ammonium citrate (FAC). Mitochondrial fragmentation via dephosphorylation of Drp1 (Ser637) and increased apoptotic neuronal death were observed in FAC-stimulated HT-22 cells. Furthermore, the levels of intracellular calcium (Ca2+) were increased by iron overload. Notably, chelation of intracellular Ca2+ rescued mitochondrial fragmentation and neuronal cell death. In addition, iron overload activated calcineurin through the Ca2+/calmodulin and Ca2+/calpain pathways. Pretreatment with the calmodulin inhibitor W13 and the calpain inhibitor ALLN attenuated iron overload-induced mitochondrial fragmentation and neuronal cell death. Therefore, these findings suggest that Ca2+-mediated calcineurin signals are a key player in iron-induced neurotoxicity by regulating mitochondrial dynamics. We believe that our results may contribute to the development of novel therapies for iron toxicity related neurodegenerative disorders

ISSN 

0300-483X

Link 

http://dx.doi.org/10.1016/j.tox.2016.07.022

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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